Some Selective Serotonin Reuptake Inhibitors Inhibit Dynamin I Guanosine Triphosphatase (GTPase)(Biochemistry)

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概要

• 論文の詳細を見る

• Neuronal dynamin I plays a critical role in the recycling of synaptic vesicles, and thus in nervous system function. We expressed and purified dynamin I to explore potentially clinically useful endocytosis inhibitors and to examine the mechanism of their action. We estimated the IC_<50> of nineteen psychotropic drugs for dynamin I. The IC_<50> values of two selective serotonin reuptake inhibitors (sertraline and fluvoxamine) were 7.3 ±1.0 and 14.7±1.6 μM, respectively. Kinetic analyses revealed that fluvoxamine is a noncompetitive inhibitor of dynamin I guanosine triphosphatase (GTPase) with respect to guanosine 5'-triphosphate (GTP) and a competitive inhibitor with respect to L-phosphatidylserine (PS). Fluvoxamine may compete with PS for binding to the pleckstrin homology domain of dynamin I. On the other hand, sertraline was a mixed type inhibitor with respect to both GTP and PS. Our results indicate that sertraline and fluvoxamine may regulate the transportation of neurotransmitters by modulating synaptic vesicle endocytosis via the inhibition of dynamin I GTPase.

• 社団法人日本薬学会の論文
• 2008-08-01

著者

• Nakashima Hideki

  Department of Microbiology and Immunologu,Kagoshima University Dental School

• Takahashi Kiyofumi

  Department Of Neuropsychiatry St. Marianna University School Of Medicine

• OTOMO Masahiro

  Department of Neuropsychiatry, St. Marianna University School of Medicine

• MIYOSHI Hiroshi

  Department of Microbiology, St. Marianna University School of Medicine

• OSADA Kenichi

  Department of Neuropsychiatry, St. Marianna University School of Medicine

• YAMAGUCHI Noboru

  Department of Neuropsychiatry, St. Marianna University School of Medicine

• Osada Kenichi

  Department Of Neuropsychiatry St. Marianna University School Of Medicine

• Otomo Masahiro

  Department Of Neuropsychiatry St. Marianna University School Of Medicine

• Miyoshi Hiroshi

  Department Of Microbiology St. Marianna University School Of Medicine

• Miyoshi Hiroshi

  Department Of Anesthesiology Nagasaki University School Of Medicine

• Nakashima Hideki

  Department Of Advanced Energy Engineering Science Interdisciplinary Graduate School Of Engineering S

• Yamaguchi Noboru

  Department Of Neuropsychiatry St. Marianna University School Of Medicine

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